Acetic Acid → 1-{Dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}urea

HRID 2207413ノート

反応式

HRID 2207413 の反応式
[O-:1][C:2]#[N:3].[K+].[NH2:5][C:6]([CH:34]1[CH2:36][CH2:35]1)([CH:31]1[CH2:33][CH2:32]1)[C:7]1[N:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]([NH:20][C:21]3[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=3)[CH:16]=[C:17]([CH3:19])[CH:18]=2)=[CH:9][CH:8]=1.C1COCC1.C(O)(=O)C>C([O-])(O)=O.[Na+].O>[CH:31]1([C:6]([CH:34]2[CH2:36][CH2:35]2)([C:7]2[CH:8]=[CH:9][C:10]([C:13]3[CH:14]=[C:15]([NH:20][C:21]4[N:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][N:22]=4)[CH:16]=[C:17]([CH3:19])[CH:18]=3)=[CH:11][N:12]=2)[NH:5][C:2]([NH2:3])=[O:1])[CH2:33][CH2:32]1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 11378442Potassium cyanateHCID 118092744N-(3-{6-[amino(dicyclopropyl)methyl]pyridin-3-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

生成物 1

HCID 1180926411-{Dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}urea

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

Potassium cyanate (71.1 mg, 0.876 mmol) was added to a mixture of N-(3-{6-[amino(dicyclopropyl)methyl]pyridin-3-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (257 mg, 0.584 mmol), THF (4.00 mL), acetic acid (0.050 ml, 0.876 mmol), and water (2.00 mL) and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with saturated aqueous NaHCO3 (20.0 mL) and extracted with ethyl acetate (50.0 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0-20% methanol in ethyl acetate) and the isolated material was then triturated with ethyl acetate (4.00 mL) and methanol (0.50 mL) to yield 1-{dicyclopropyl[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)pyridin-2-yl]methyl}urea. MS APCI calc'd for C25H26F3N6O [M+H]+ 483. found 483. 1H NMR (500 MHz, CD3OD) δ11.08 (s, 1H), 9.65 (d, J=5.3 Hz, 1H), 9.49 (d, 1H), 8.74 (s, 1H), 8.68 (d, J=11.2 Hz, 1H), 8.47-8.19 (m, 2H), 8.08 (d, J=5.2 Hz, 1H), 7.98 (s, 1H), 6.87 (s, 1H), 6.24 (s, 2H), 3.16 (s, 4H), 2.26 (s, 2H), 1.26 (d, J=25.7 Hz, 3H), 1.10 (d, J=6.0 Hz, 4H).

後処理

  1. extractionextracted with ethyl acetate (50.0 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (0-20% methanol in ethyl acetate)
  7. customthe isolated material was then triturated with ethyl acetate (4.00 mL) and methanol (0.50 mL)

出典と根拠

ORDレコード
ord-38523118f55c48c5b02bec89fdf89e29
出典データセット
uspto-grants-2016_06
特許番号
US09376418B2

反応ノート

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